Abstract: FR-PO723
Adriamycin-Induced Nephropathy Is Robust in N and Modest in J Substrain of C57BL/6 Mice
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1304 Glomerular Diseases: Podocyte Biology
Authors
- Bryant, Claire, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
- Cianciolo, Rachel, The Ohio State University, Columbus, Ohio, United States
- Govindarajan, Rajgopal, The Ohio State University, Columbus, Ohio, United States
- Agrawal, Shipra, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
Background
Adriamycin (ADR)-induced nephropathy remains the leading model to study human primary focal segmental glomerulosclerosis (FSGS), a common pathway for podocyte damage and glomerular loss of function that leads to chronic kidney disease. However, the use of this model for reverse genetics is limited by historical categorization of C57BL/6 mice as an ADR-resistant strain, which is also the most common genetically modified strain. Additionally, conflicting reports exist utilizing C57BL/6 for ADR-nephrosis due to lack of understanding of substrain differences (J/N) and variability in ADR dosage, timing, and frequency to induce damage. We have undertaken a systematic approach to elucidate the specifics of ADR-nephrosis in C57BL/6 N and J substrains.
Methods
We induced nephropathy with 2 doses of ADR, and measured albuminuria for 6 weeks. Additional serum chemistry was performed along with histological evaluations. Podocyte injury markers were evaluated to assess the damage of glomerular filtration barrier.
Results
Our findings revealed induction of robust and modest proteinuria in N and J substrains, respectively. The serum creatinine levels were elevated in N, but not J substrain. Both the substrains showed reduction in body weight with N greater than J, although mortality remained at 0% in both substrains. Histological analysis showed worse renal lesions in the N than the J substrain. Podocyte markers synaptopodin, nephrin, podocin, and WT1 were reduced to a greater extent in the N than the J substrain.
Conclusion
In summary, we provide the nephrology community with a reproducible mouse model for FSGS, in a strain otherwise assumed to be ADR-resistant and highlight the differences between J and N substrains. This enables future studies, especially concerning genetically manipulated animal models in C57BL/6.